The present invention generally relates to the delivery of medicaments and other agents. More specifically, the present invention relates to the delivery of medicaments and agents using chewing gum formulations and methods for producing such products.
It is of course known to provide agents to individuals for various purposes. These agents can be used to treat diseases and as such are typically referred to as drugs or medicaments. Likewise, the drugs or medicaments can be used for prophylactic purposes. Still, it is known to provide agents to an individual for a variety of non-medical purposes including enhancing performance or maintaining or initiating alertness. There are a great variety of such agents. These agents run the gamut from stimulants such as caffeine to drugs such as analgesics, tranquilizers, cardiovascular products, insulin, etc. Some such agents are taken on an as needed basis while other agents must be taken at regular intervals by the individual.
Typically, drugs (medicaments) are administered parenterally or enterally. Of course, parenteral administration is the administration of the drug intravenously directly into the blood stream. Enteral refers to the administration of the drug into the gastrointestinal tract. In either case, the goal of the drug administration is to move the drug from the site of administration towards the systemic circulation.
Except when given intravenously, a drug must traverse several semipermeable cell membranes before reaching general circulation. These membranes act as a biological barrier that inhibits the passage of drug molecules. There are believed to be four processes by which drugs move across a biological barrier: passive diffusion; facilitated diffusion; active transport; and pinocytosis.
Passive diffusion is the transport across the cell membrane wherein the driving force for the movement is the concentration gradient of the solute. In orally administered drugs, this absorption occurs in the small intestines. Facilitated diffusion is believed to be based on a carrier component that combines reversibly with the substrate molecule at the cell membrane exterior. The carrier substrate complex diffuses rapidly across the membrane with release of the substrate at the interior surface. Active transport requires an energy expenditure by the cell and appears to be limited to agents with structural similarities to normal body constituents. These agents are usually absorbed from specific sites in the small intestines. Pinocytosis refers to the engulfing of particulars or fluid by a cell. It is believed to play a minor role in drug transport. Merck Manual, 16th Edition, pp. 2598-2599.
In determining the efficacy of a drug and the effectiveness of the use of a drug to treat a disease, drug absorption is a critical concern. Drug absorption refers to the process of drug movement from the site of administration toward the systemic circulation.
Oral administration of drugs is by far the most common method. When administered orally, drug absorption usually occurs due to the transport of cells across the membranes of the epithelial cells within the gastrointestinal tract. Absorption after oral administration is confounded by numerous factors. These factors include differences down the alimentary canal in: the luminal pH; surface area per luminal volume; perfusion of tissue, bile, and mucus flow; and the epithelial membranes. See Merck Manual at page 2599.
A further issue effecting the absorption of orally administered drugs is the form of the drug. Most orally administered drugs are in the form of tablets or capsules. This is primarily for convenience, economy, stability, and patient acceptance. Accordingly, these capsules or tablets must be disintegrated or dissolved before absorption can occur. There are a variety of factors capable of varying or retarding disintegration of solid dosage forms. Further, there are a variety of factors that effect the dissolution rate and therefore determine the availability of the drug for absorption. See Merck Manual at page 2600.
Parenteral administration allows for the direct placement of the drug into the blood stream. This usually insures complete delivery of the dose to the general circulation. However, administration by a route that requires drug transfer through one or more biologic membranes to reach the blood stream precludes a guarantee that all of the drug will eventually be absorbed. Even with parenteral administration, because capillaries tend to be highly porous, the perfusion (blood flow/gram of tissue) is a major factor in the rate of absorption. Thus, the injection site can markedly influence a drugs"" absorption rate; e.g., the absorption rate of diazepam injected IM into a site with poor blood flow can be much slower than following an oral dose. See Merck Manual at page 2601.
Not only is drug absorption an issue in drug delivery but also the bioavailability of the drug is also critical. Bioavailability is defined as the rate at which and the extent to which the active moiety (drug or metabolite) enters the general circulation, thereby gaining access to the site of action. Bioavailability depends upon a number of factors, including how a drug product is designed and manufactured, its physicochemical properties, and factors that relate to the physiology and pathology of the patient. See Merck Manual at page 2602.
When a drug rapidly dissolves from a drug product and readily passes across membranes, absorption from most site administration tends to be complete. This is not always the case for drugs given orally. Before reaching the vena cava, the drug must move down the alimentary canal and pass through the gut wall and liver, which are common sites of drug metabolism. Thus, the drug may be metabolized before it can be measured in the general circulation. This cause of a decrease in drug input is called the first pass effect. A large number of drugs show low bioavailability owing to an extensive first pass metabolism. The two other most frequent causes of low bioavailability are insufficient time in the GI tract and the presence of competing reactions. See Merck Manual at page 2602.
Bioavailability considerations are most often encountered for orally administered drugs. Differences in bioavailability can have profound clinical significance.
Although parenteral administration does provide a method for eliminating a number of the variables that are present with oral administration, parenteral administration is not a preferable route. Typically, parenteral administration requires the use of medical personnel and is just not warranted nor practical for the administration of most agents and drugs, e.g., analgesics. Even when required, parenteral administration is not preferred due to patient concerns including comfort, infection, etc., as well as the equipment and costs involved. However, despite best efforts certain therapies require parenterally injected drugs. For example, research for decades has focused on an attempt to deliver insulin to an individual through a non-parenteral means. Despite such efforts, today insulin is still only administered intravenously.
In producing products for delivering medicaments and other agents to an individual, it may be critical that a predefined amount of medicament or agent is delivered per dose of the product. This allows the physician and/or patient to determine the amount of product to ingest and insure that a safe and effective level of medicament or agent is delivered. If the medicament or agent is located in a coating of the product it is necessary to ensure that definite levels of coating are present in each product. This requires a manufacturing process that allows for the accurate production of coated products.
A still further issue vis-a-vis drug delivery, and most specifically oral drug delivery, is taste. Many over the counter and pharmaceutical products are not available in a chewable form due to taste problems. Such products include, for example, excedrin, pseudoephedrin, and Ma Huang/guarana diet pills.
Thus, there is a need for an improved method of delivering drugs and agents to an individual.
The present invention provides improved methods for manufacturing products for delivering a medicament or agent to an individual as well as such products. To this end, a compressible excipient is tableted and then coated to produce a coated product including a medicament or agent. The medicament or agent is present within the coating or shell that substantially encloses the tableted compressible excipient. It has been found that by tableting the compressible excipient that a specifically defined coating can be provided, providing a predetermined and controllable level of medicament or agent.
The excipient can be, by way of example and not limitation, dextrose, sucrose, or other saccharides, sorbitol, mannitol, iso-malitol, other compressible sugar alcohols, or combinations thereof.
Improved formulations including medicaments or agents are also provided by the present invention.
To this end, the present invention provides a product including a tableted compressible excipient. The tableted compressible excipient is substantially surrounded by a coating. The coating includes a medicament or agent and comprises at least 50% by weight of the product.
In an embodiment, the coating includes a masking agent to assist in improving the organoleptic properties of the coating containing the medicament. The masking agent may be chosen from the group consisting of: sucralose; zinc gluconate; ethyl maltol; glycine; acesulfame-K; aspartame; saccharin; fructose; xylitol; spray dried licorice root; glycerrhizine; dextrose; sodium gluconate; glucono delta-lactone; ethyl vanillin; vanillin; normal and high-potency sweeteners; and a variety of appropriate flavors.
In an embodiment, the coating includes a high-intensity sweetener. In a further embodiment, the high-intensity sweetener is chosen from the group consisting of aspartame, sucralose, and acesulfame-K.
In an embodiment, the compressible excipient is chosen from the group consisting of dextrose, sucrose, sorbitol, manitol, and combinations of same.
In an embodiment, the coating comprises 50% to 75% by weight of the product.
In an embodiment, the coating is a recrystallized granular coating.
In an embodiment, the coating is an amorphous coating.
In an embodiment, the coating is a powder coating.
In an embodiment, the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antacids; antihistamines; decongestants; anti-inflammatories; antibiotics; antivirals; psychotherapeutic agents; insulin; nutraceuticals; nutritional supplements; and cardiovascular agents.
In another embodiment of the present invention a method of drug delivery is provided. The method comprising the steps of: providing a product that includes a compressible excipient that is substantially surrounded by a coating, the coating includes a medicament; chewing the product to cause the medicament to be released from the product into the buccal cavity of the chewer; and continuing to chew the product thereby creating a fluid pressure causing the medicament to enter the systemic system of the chewer through the oral mucosa contained in the buccal cavity.
In an embodiment of the method, the agent is a medicament. In an embodiment of the method, the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antihistamines; decongestants; antacids; anti-inflammatories; antibiotics; antivirals; psychotherapeutic agents; insulin; nutraceuticals; nutritional supplements; and cardiovascular agents.
In yet another embodiment of the present invention a method of delivering a medicament is provided. The method comprising the steps of: providing a product including a coating that comprises at least 50% by weight of the product and surrounds a tableted compressible excipient. The coating includes a medicament; and chewing the product.
In a still further embodiment of the present invention a product containing a medicament or agent is provided. The product includes a tableted compressible excipient center. The coating surrounds the tableted center and includes a medicament. The coating comprising at least 50% by weight of the product. The coating includes taste masking agents.
Moreover, in an embodiment of the present invention, a method of manufacturing a product containing a medicament or agent is provided. The method comprising the steps of: preparing a tableted compressible excipient center; and coating the tableted center with a powder and a syrup to create a coated product, at least one of the powder or syrup portion including a medicament or agent.
In an embodiment the powder and syrup are coated on the compressible excipient in alternating steps until a sufficient coating has been built up.
In an embodiment the coating has a polished finish.
Accordingly, an advantage of the present invention is to provide new methods for manufacturing products for delivering medicaments or agents to an individual.
Furthermore, an advantage of the present invention is to provide an improved product containing a medicament.
Additionally, an advantage of the present invention is to provide a method for administering medicaments that is more palatable than current methods.
Still further, an advantage of the present invention is to provide a method of delivering medicaments to an individual that provides for increase absorption and bioavailability as compared to medicaments that are designed to be absorbed in the GI tract.
Further, an advantage of the present invention is to provide a method of administering a medicament or agent to an individual at a lower level than is typically administered orally while still achieving the same effect.
Furthermore, an advantage of the present invention is to provide a method for administering medicaments or agents to an individual that heretofore were administered parenterally.
Another advantage of the present invention is to provide a method for manufacturing products including medicaments or agents in the coating.
Moreover, an advantage of the present invention is to provide an improved method for drug delivery.
Further, an advantage of the present invention is to provide a chewable product that contains an agent that heretofore could not be provided in a chewable form that was palatable.
Still, an advantage of the present invention is to provide a method for ensuring that a coated product that includes a medicament has a precise level of medicament.
An advantage of the present invention is that a coated product is provided wherein the coating can absorb or lose moisture without apparent degradation.
Further, an advantage of the present invention is that a coated chewing gum product including medicament is provided having an extended shelf-life.
Furthermore, an advantage of the present invention is that it can produce medicament-containing products having precise sizes and shapes.
Another advantage of the present invention is to provide a method of controlling the amount of agent containing coating that is used on a coated product.
Additional features and advantages of the present invention will be described in and apparent from the detailed description of the presently preferred embodiments and the figures.